The proposed research deals with changes in nuclear protein composition and with post-synthetic modifications of nuclear proteins during early stages of carcinogenesis in the colonic epithelium. We have identified nuclear proteins which are selectivity synthesized soon after exposure of animals to 1,2-dimethyl-hydrazine (DMH). One of these, called TNP1, has been electrophoretically characterized, purified and analyzed. It is a DNA-binding protein of MW ca. 44,000, and it appears to be localized in the nuclei of the dividing cell population of colonic adenocarcinomas. Similar proteins occur in human colonic adenocarcinomas and in derivative cell lines (such as HT-29), but TNP1 has not been detected in nuclei from non-malignant polyps in individuals with familial polyposis coli. The appearance of TNP1 correlates with the spread of the malignant proliferative zone around a primary tumor. Although TNP1 is one of the major non-histone protein classes in the nuclei of DMH tumors in SWR/J mice, it is not present in the nuclei of the colonic epithelium of the DMH-resistant AKR/J strain after equivalent exposures to the carcinogen. Because of its close correlation with the malignant state, we have begun to purify the human colonic protein corresponding to TNP1 in rodent adenocarcinomas. Antibodies to the purified human protein will be employed in immunofluorescence assays for its detection in single cells. This may permit early diagnosis of malignant transformation in individuals at high risk for colon cancer. Some of the earliest changes in nuclear protein metabolism in DMH-treated animals involve post-synthetic modifications of the polypeptide chain. Our major focus of interest is the specificity of phosphorylation of nuclear proteins, which is altered in carcinogen-treated animals, and with changes in kinase activities.